Cationic Photosensitizer Research Articles

Cationic Chalcogenoviologen Derivatives for Photodynamic Antimicrobial Therapy and Skin Regeneration.

A series of water-soluble cationic chalcogenoviologen-based photosensitizers for photodynamic antimicrobial therapy (PDAT) is reported. The Se-containing derivatives (SeMV2+ ) 5 b and 6 b showed good antimicrobial activities due to the presence of chalcogen atoms and a cationic scaffold. The former efficiently enhanced the generation of reactive oxygen species (ROS), and the latter facilitated the ROS delivery to bacteria, resulting in their death. Interestingly, alkyl-modified photosensitizers showed higher antimicrobial activities than commonly reported photosensitizers with quaternary ammonium (QA) groups. In particular, the SeMV2+ (6 b) with excellent antibacterial activities efficiently promoted the healing of infected wounds in mice. Simple yet novel, nontoxic and biocompatible chalcogenoviologens provided a promising strategy to develop new efficient photosensitizers for photodynamic antimicrobial therapy and skin regeneration.

BODIPY-embedded electrospun materials in antimicrobial photodynamic inactivation.

Drug-resistant pathogens, particularly those that result in hospital acquired infections (HAIs), have emerged as a critical priority for the World Health Organization. To address the need for self-disinfecting materials to counter the threat posed by the transmission of these pathogens from surfaces to new hosts, here we investigated if a cationic BODIPY photosensitizer, embedded via electrospinning into nylon and polyacrylonitrile (PAN) nanofibers, was capable of inactivating both bacteria and viruses via antimicrobial photodynamic inactivation (aPDI). Materials characterization, including fiber morphology and the degree of photosensitizer loading, was assessed by scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and UV-visible diffuse reflectance spectroscopy (UV-Vis DRS), and demonstrated that the materials were comprised of nanofibers (125-215 nm avg. diameter) that were thermostable to >300 °C. The antimicrobial potencies of the resultant Nylon-BODIPY(+) and PAN-BODIPY(+) nanofiber materials were evaluated against four strains of bacteria recognized by the World Health Organization as either critical or high priority pathogens: Gram-positive strains methicillin-resistant S. aureus (MRSA; ATCC BAA-44) and vancomycin-resistant E. faecium (VRE; ATCC BAA-2320), and Gram-negative strains multidrug-resistant A. baumannii (MDRAB; ATCC BAA-1605) and NDM-1 positive K. pneumoniae (KP; ATCC BAA-2146). Our results demonstrated the detection limit (99.9999%; 6 log units reduction in CFU mL-1) photodynamic inactivation of three strains upon illumination (30-60 min; 40-65 ± 5 mW cm-2; 400-700 nm): MRSA, VRE, and MDRAB, but only minimal inactivation (47-75%) of KP. Antiviral studies employing PAN-BODIPY(+) against vesicular stomatitis virus (VSV), a model enveloped virus, revealed complete inactivation. Taken together, the results demonstrate the potential for electrospun BODIPY(+)-embedded nanofiber materials as the basis for pathogen-specific anti-infective materials, even at low photosensitizer loadings.

Tumor-targeting photodynamic therapy based on folate-modified polydopamine nanoparticles.

BackgroundPhotodynamic therapy (PDT), a clinical anticancer therapeutic modality, has a long history in clinical cancer treatments since the 1970s. However, PDT has not been widely used largely because of metabolic problems and off-target phototoxicities of the current clinical photosensitizers.PurposeThe objective of the study is to develop a high-efficiency and high-specificity carrier to precisely deliver photosensitizers to tumor sites, aiming at addressing metabolic problems, as well as the systemic damages current clinical photosensitizers are known to cause.MethodsWe synthesized a polydopamine (PDA)-based carrier with the modification of folic acid (FA), which is to target the overexpressed folate receptors on tumor surfaces. We used this carrier to load a cationic phthalocyanine-type photosensitizer (Pc) and generated a PDA-FA-Pc nanomedicine. We determined the antitumor effects and the specificity to tumor cell lines in vitro. In addition, we established human cancer-xenografted mice models to evaluate the tumor-targeting property and anticancer efficacies in vivo.ResultsOur PDA-FA-Pc nanomedicine demonstrated a high stability in normal physiological conditions, however, could specifically release photosensitizers in acidic conditions, eg, tumor microenvironment and lysosomes in cancer cells. Additionally, PDA-FA-Pc nanomedicine demonstrated a much higher cellular uptake and phototoxicity in cancer cell lines than in healthy cell lines. Moreover, the in vivo imaging data indicated excellent tumor-targeting properties of PDA-FA-Pc nanomedicine in human cancer-xenografted mice. Lastly, PDA-FA-Pc nanomedicine was found to significantly suppress tumor growth within two human cancer-xenografted mice models.ConclusionOur current study not only demonstrates PDA-FA-Pc nanomedicine as a highly potent and specific anticancer agent, but also suggests a strategy to address the metabolic and specificity problems of clinical photosensitizers.

Phenotypic Resistance in Photodynamic Inactivation Unravelled at the Single Bacterium Level.

Herein we report a simple fluorescence microscopy methodology that, jointly with four photosensitizers (PSs) and a cell viability marker, allows monitoring of phenotypic bacterial resistance to photodynamic inactivation (PDI) treatments. The PSs, composed of BODIPY dyes, were selected according to their ability to interact with the cell wall and the photoinactivating mechanism involved (type I or type II). In a first approach, the phenotypic heterogeneity allowing bacteria to persist during PDI treatment was evaluated in methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli as Gram-positive and Gram-negative models, respectively. By means of propidium iodide (PI), we monitored with spatiotemporal resolution cell viability at the single bacterium level. All the PSs were effective at inactivating pathogens; however, the cationic nonhalogenated PS (compound 1) surpassed the others and was capable of photoinactivating E. coli even under optimal growth conditions. Compound 1 was further tested on two other Gram-negative strains, Pseudomonas aeruginosa and Klebsiella pneumoniae, with outstanding results. All bacterial strains used here are well-known ESKAPE pathogens, which are the leading cause of nosocomial infections worldwide. Thorough data analysis of individual cell survival times revealed clear phenotypic variation expressed in the cell wall that affected PI permeation and thus its intercalation with DNA. For the same bacterial sample, death times may vary from seconds to hours. In addition, the PI incorporation time is also a parameter governed by the phenotypic characteristics of the microbes. Finally, we demonstrate that the results gathered for the bacteria provide direct and unique experimental evidence that supports the time-kill curve profiles.

Revealing the dynamics and energetics of interaction of a cationic biological photosensitizer within a bile salt aggregate.

The present investigation reports a detailed characterization of the interaction of a cationic photosensitizer, phenosafranin (PSF) with sodium deoxycholate (NaDC) bile salt aggregates based on spectroscopic and calorimetric techniques. Our explicit spectroscopic results not only establish the occurrence of PSF-NaDC binding interaction, but also reveal marked lowering of micropolarity at the interaction site (ET(30) = 55.97 kcal mol-1 in the presence of NaDC as compared to ET(30) = 63.1 kcal mol-1 in bulk aqueous buffer). A thorough mathematical analysis of the fluorescence depolarization results based on the two-step and wobbling in cone model yields critical insight into the complex rotational relaxation dynamics of the bound drug. The impartation of motional restriction on the PSF molecules within the bile salt aggregates is evidenced from enhancement of average rotational correlation time from <τr> = 136 ps in aqueous buffer to 1.11 ns with added NaDC (8.0 mM). This is further supported from a high value of the generalized order parameter (S = 0.81) as well as the diffusion coefficient (Dw = 1.40 × 1012 s-1). Furthermore, our extensive calorimetric investigation unveils the complicated thermodynamics of the interaction process in terms of predominant entropic contribution over the enthalpic part in the lower temperature regime (TΔS = 18.84 ± 1.13 kJ mol-1, ΔH = -5.82 ± 0.35 kJ mol-1 at 288 K) with subsequent reversal of the relative contributions with increasing temperature (TΔS = 7.54 ± 0.39 kJ mol-1, ΔH = - 17.09 ± 0.90 kJ mol-1 at 318 K). The instrumental role of the hydrophobic effect underlying the PSF-NaDC interaction is characterized by a negative heat capacity change (ΔCp = -364 J mol-1 K-1). An intriguing thermodynamic feature in terms of enthalpy-entropy compensation (with increasing temperature ΔG remains almost constant while ΔH and TΔS vary significantly) aptly corroborates the aforesaid argument and establishes an appreciable hydrophobic contribution to the overall binding energies.

Degradable Supramolecular Photodynamic Polymer Materials for Biofilm Elimination.

In this work, we fabricated a degradable supramolecular photodynamic polymer (SPP) with an enhanced efficiency of biofilm elimination. The small-molecule photosensitizer, a cationic porphyrin derivative, was grafted to a block polymer backbone (BPB) through a host-guest interaction and metal coordination. The locally enriched cationic photosensitizer in SPP endows a high efficiency to disrupt biofilms due to the generated reactive oxygen species (ROS) around the bacteria under white light illumination, while reducing the cytotoxicity to mammalian cells. After cucurbit[7]uril was added as a competitive agent, the photosensitizer could be disassociated from the BPB and the antibacterial ability was reduced; also the SPP could be further degraded. As a consequence, the supramolecular photodynamic polymer may become a very promising material for biofilm elimination with an enhanced antibacterial efficacy and degradability to fight against drug-resistant bacteria.

Effect of hyaluronic acid on the State and photoactivity of Zn(II) phthalocyanine cationic derivative in mixed aqueous solutions

The effect of the hyaluronic acid (HA) on the state and photoactivity of the cationic phthalocyanine photosensitizer in mixed solutions was studied by UV–vis absorption, fluorescence, FT-IR spectroscopy and dynamic light scattering methods. As a cationic photosensitizer, the Cholosens® (ChS) was used, which is Zn phthalocyanine choline derivative and is designed for photodynamic therapy of cancer and infectious diseases. It was found that the state of mixed solutions depends on the molar ratio HA/ChS. In mixtures with HA/ChS ≤ 7.0, with an increase in the HА content the fluorescence intensity decreases up to complete quenching at HA/ChS = 7.0 and precipitation is observed due to the formation of a supramolecular complex. The hydrodynamic radius and zeta potential of complex primary particles in the metastable state preceding the phase separation are determined. Mixtures with HA/ChS > 7.5 are stable solutions with no signs of phase separation. The fluorescence intensity increases with an increase in HA/ChS from 7.0 to 20, and with a further increase in the HА content remains constant and is about 80% relative to ChS fluorescence without HA. Gamma-irradiation of HA causes a decrease in its ability to complexate with ChS due to a decrease in the polymer chain length.

Preliminary evaluation of the positively and negatively charge effects of tetra-substituted porphyrins on photoinactivation of rapidly growing mycobacteria

This manuscript reports, at the first time, the photoinactivation evaluation of tetra-cationic and anionic porphyrins as photosensitizers (PS) for the photodynamic inactivation (PDI) of rapidly growing mycobacteria strains. Two different charged porphyrin groups were obtained commercially. PDI experiments in the strains Mycobacterium massiliense e Mycobacterium fortuitum conducted with adequate concentration (without aggregation) of photosensitizer under white light at a fluence rate of 50 mW/cm2 over 90 min showed that the most effective PS caused a 100 times reduction in the concentration of viable mycobacteria. The present results show that porphyrin with positively charge are more efficient PS than anionic porphyrin (negatively charged) against M. massiliense e M. fortuitum. It is also clear that the effectiveness of the molecule as PS for PDI studies with mycobacteria is strongly related with the porphyrin peripheral charge, and consequently their solubility in physiological media. Cationic PSs might be promising anti-mycobacteria PDI agents with potential applications in medical clinical cases and bioremediation.

Unsaturation of the phospholipid side-chain influences its interaction with cyclodextrins: A spectroscopic exploration using a phenazinium dye

The interaction of a cationic photosensitizer Safranin-O with liposome membranes having similar surface charge (negative) but differing in the presence of saturation on the lipid side-chain has been studied. To this end, dimyristoyl-l-R-phosphatidylglycerol (DMPG) and 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG) phospholipids were employed to prepare small unilamellar vesicles. The dye is found to bind in the headgroup region of both the liposome membranes with significantly higher affinity to DOPG lipid containing unsaturated side chain. The effects of various cyclodextrins (CDs) on the stability of the probe-bound liposome membranes have also been investigated using steady-state and picosecond-resolved fluorescence as well as dynamic light scattering techniques. The modulations of the fluorescence properties of the lipid-bound dye were exploited to rationalize the membrane destabilization following interaction with the cyclodextrins. Experimental results reveal the selective interaction of DMPG membrane with CDs leading to rupture of the integrated structure of the liposome units accompanying release of the bound probe to the bulk aqueous phase. On the contrary, no discernible interaction of the CDs was observed with DOPG liposome membrane. Our results also show the differential extents of interaction of various CDs (α-CD, β-CD, methyl-β-CD, and γ-CD) with DMPG leading to varying degrees of release of the bound-dye molecule.

In Situ Monitoring Apoptosis Process by a Self-Reporting Photosensitizer.

Although photodynamic therapy (PDT) has thrived as a promising treatment, highly active photosensitizers (PSs) and intense light power can cause treatment overdose. However, extra therapeutic response probes make the monitoring process complicated, ex situ and delayed. Now, this challenge is addressed by a self-reporting cationic PS, named TPE-4EP+, with aggregation-induced emission characteristic. The molecule undergoes mitochondria-to-nucleus translocation during apoptosis induced by PDT, thus enabling the in situ real-time monitoring via fluorescence migration. Moreover, by molecular charge engineering, we prove that the in situ translocation of TPE-4EP+ is mainly attributed to the enhanced interaction with DNA imposed by its multivalent positive charge. The ability of PS to provide PDT with real-time diagnosis help control the treatment dose that can avoid excessive phototoxicity and minimize potential side effect. Future development of new generation of PS is envisioned.

New cationic photosensitizers: photophysical properties and results of preliminary studies of antibacterial efficacy

Polycationic derivatives of synthetic bacteriochlorin with absorption in the near infrared range are promising for the creation of photosensitizers (PS) for antimicrobial photodynamic therapy. In the present work, the photophysical and antibacterial properties of PS based on tetracationic derivatives of synthetic bacteriochlorins: hydrophilic 3-Py4BC(EtBr)4Br4 in aqueous solution and amphiphilic 3-Py4BCHP4Br4 in the dispersion of Kolliphor ELP were studied. Analysis of absorption and fluorescence in a wide range of concentrations has demonstrated low aggregation of the PS over the entire range. A high efficiency of photodynamic inactivation of Gram-positive Staphylococcus aureus and Gramnegative Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii bacteria was observed.

Innovative approach in Legionella water treatment with photodynamic cationic amphiphilic porphyrin

Abstract Legionella is an opportunistic premise plumbing pathogen that can be present in municipal and other water supplies. Building water systems may provide conditions (such as low flow, water hardness, low disinfectant residual levels and optimal temperature) that accelerate Legionella growth to levels that may result in an increased risk to public health. The standard disinfection of water systems (periodic overheating of water and chlorination) in the interest of prevention of Legionnaires' disease have often proved to be inefficient. It is therefore necessary to develop new approaches for removing Legionella from water systems. One of the new methods is antimicrobial photodynamic therapy (aPDT), which includes the combined activity of a photosensitizer (PS), molecular oxygen and visible light of appropriate wavelength to create singlet oxygen (1O2) and other oxygen reactive species (ROS) leading to the oxidation of numerous cellular components and cell death. In this study, a newly synthesized cationic, amphiphilic porphyrin TMPyP3-C17H35, was tested against Legionella in tap water. The minimal effective concentration (MEC) of PS photoinactivation test and PS uptake assay in sterile tap water were explored to determine the anti-Legionella activity. The complete inactivation of Legionella in sterile tap water was achieved with 0.024 μM of the PS. Also, the tested PS was found to be very effective in reducing Legionella growth in the sterile tap water and photoinactivation was dose-dependent. The tested PS binds well to the bacterial cell, after only 10 minutes of incubation in the dark. In conclusion, these studies indicate that TMPyP3-C17H35 is highly efficient in aPDT which leads to reducing Legionella growth in sterile tap water, and these results suggest that cationic amphiphilic photosensitizers may have a broader application in the photoinactivation of bacterial cells implicated in water disinfection.

Negatively charged metal-organic hosts with cobalt dithiolene species: improving PET processes for light-driven proton reduction through host-guest electrostatic interactions.

By incorporating 1,2-benzenedithiol as a chelator to construct cobalt dithiolene species, two negatively charged redox-active metal-organic hosts were obtained. By taking advantage of electrostatic interactions, cationic Ru-based photosensitizers were constrained to improve photoinduced electron transfer processes for efficient photocatalytic proton reduction.

NIR-excited superoxide radical procreators to eradicate tumors by targeting the lyso-membrane

NIR alkylated cationic photosensitizers targeting at lyso-membrane for eradicating tumor cells through prominent superoxide radical generation (type-I PDT) via lysosome disruption pathway.

An Insight Into the Potentiation Effect of Potassium Iodide on aPDT Efficacy.

Antimicrobial photodynamic therapy (aPDT) is gaining a special importance as an effective approach against multidrug-resistant strains responsible of fatal infections. The addition of potassium iodide (KI), a non-toxic salt, is recognized to increase the aPDT efficiency of some photosensitizers (PSs) on a broad-spectrum of microorganisms. As the reported cases only refer positive aPDT potentiation results, in this work we selected a broad range of porphyrinic and non-porphyrinic PSs in order to gain a more comprehensive knowledge about this aPDT potentiation by KI. For this evaluation were selected a series of meso-tetraarylporphyrins positively charged at meso positions or at β-pyrrolic positions and the non-porphyrinic dyes Methylene blue, Rose Bengal, Toluidine Blue O, Malachite Green and Crystal Violet; the assays were performed using a bioluminescent E. coli strain as a model. The results indicate that KI has also the ability to potentiate the aPDT process mediated by some of the cationic PSs [Tri-Py(+)-Me, Tetra-Py(+)-Me, Form, RB, MB, Mono-Py(+)-Me, β-ImiPhTPP, β-ImiPyTPP, and β-BrImiPyTPP] allowing a drastic reduction of the treatment time as well as of the PS concentration. However, the efficacy of some porphyrinic and non-porphyrinic PSs [Di-Py(+)-Me opp, Di-Py(+)-Me adj, Tetra-Py, TBO, CV, and MG] was not improved by the presence of the coadjuvant. For the PSs tested in this study, the ones capable to decompose the peroxyiodide into iodine (easily detectable by spectroscopy or by the visual appearance of a blue color in the presence of amylose) were the most promising ones to be used in combination with KI. Although these studies confirmed that the generation of 1O2 is an important fact in this process, the PS structure (charge number and charge position), aggregation behavior and affinity for the cell membrane are also important features to be taken in account.

In vitro photodynamic inactivation (PDI) of pathogenic germs inducing onychomycosis.

Onychomycosis is a fungal nail infection caused primarily by the dermatophytes Trichophyton rubrum and Trichophyton interdigitale or, less frequently, by molds like Aspergillus spp. and Scopulariopsis brevicaulis. Photodynamic treatment of onychomycosis is considered a promising future therapy to overcome the frequent failure of currently used antifungals. In this study, we tested the potential of three photosensitizers for photodynamic inactivation of the onychomycosis causing pathogens T. rubrum, T. interdigitale and S. brevicaulis. Photosensitizers used are 10,15,20-Tetrakis(1-methylpyridinium-4-yl) porphyrintetra(p-toluenesulfonate) (TMPyP), 5,10,15-tris-(1-methylpyridinium-2-yl)corrolato-(trans-dihydroxo)phosphorus(V) (PCor+) and 2',4',5',7'-tetrabromo-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one (Eosin Y). The phototoxic effects caused by the cationic photosensitizers (PCor+ and TMPyP) were tested on suspension cultures of spores as well as on fungi during growth on surfaces where both photosensitizers cause high phototoxicity. The anionic Eosin Y was tested on surface-growing fungi only and induces remarkable phototoxic effects on dermatophytes and molds. In all cases, no spore regrowth was detected after PDI. This study is considered a first step towards successful and cost efficient treatment of onychomycosis.

Photodynamic inactivation of bacteria to decolonize meticillin-resistant Staphylococcus aureus from human skin.

To prevent infections that arise from the skin surface it is necessary to decolonize human skin prior to any proposed treatment or surgical intervention. Photodynamic inactivation of bacteria (PIB) uses cationic photosensitizers that attach to the surface of bacteria, generate reactive oxygen species on light irradiation and thereby kill bacteria via oxidative mechanisms. To evaluate the potential and the safety of PIB for decolonization of bacteria from skin. PIB with the new photosensitizer SAPYR [2-((4-pyridinyl)methyl)-1H-phenalen-1-one chloride] was initially tested against different bacterial species in vitro. Then, ex vivo porcine skin samples were used as a model for decolonization of different bacteria species. The numbers of viable bacteria were quantified and the mitochondrial activity of skin cells was histologically analysed (using nitroblue tetrazolium chloride, NBTC). The same procedure was performed for human skin and meticillin-resistant Staphylococcus aureus (MRSA). The in vitro studies showed a 5 log10 reduction of all tested bacterial species. On ex vivo porcine skin samples, PIB reduced the viability of all tested bacterial species by at least 3 log10 steps. On human skin samples ex vivo, PIB reduced the number of viable MRSA by maximal 4·4 log10 steps (1000 μmol L-1 SAPYR, incubation time 10 min, 60 J cm-2 ). NBTC staining showed normal mitochondrial activity in skin cells after all PIB modalities. The results of this study show that PIB can effectively and safely kill bacteria like MRSA on the skin surface and might have the potential of skin decolonization in vivo.

Synthetic, small-molecule photoantimicrobials - a realistic approach.

The search for suitable, low-molecular weight photoantimicrobials for use in infection control has strong foundations in conventional antiseptic research from the early-mid 20th Century. Many examples of dyes exist having conventional antimicrobial activity among the azine, acridine and triphenylmethane families which have since also been found to exhibit photosensitising capabilities. The prior employment of these examples in human antisepsis provides a practical basis in terms of low host toxicity, while extant structure-activity relationships for conventional antimicrobial activity can support the development of similar relationships for photoactivated cell killing. The range of chromophores covered allows progress to be made both in topical and deeper, fluid-involved infections.

Nanoscale metal-organic frameworks for mitochondria-targeted radiotherapy-radiodynamic therapy

Selective delivery of photosensitizers to mitochondria of cancer cells can enhance the efficacy of photodynamic therapy (PDT). Though cationic Ru-based photosensitizers accumulate in mitochondria, they require excitation with less penetrating short-wavelength photons, limiting their application in PDT. We recently discovered X-ray based cancer therapy by nanoscale metal–organic frameworks (nMOFs) via enhancing radiotherapy (RT) and enabling radiodynamic therapy (RDT). Herein we report Hf-DBB-Ru as a mitochondria-targeted nMOF for RT-RDT. Constructed from Ru-based photosensitizers, the cationic framework exhibits strong mitochondria-targeting property. Upon X-ray irradiation, Hf-DBB-Ru efficiently generates hydroxyl radicals from the Hf6 SBUs and singlet oxygen from the DBB-Ru photosensitizers to lead to RT-RDT effects. Mitochondria-targeted RT-RDT depolarizes the mitochondrial membrane to initiate apoptosis of cancer cells, leading to significant regression of colorectal tumors in mouse models. Our work establishes an effective strategy to selectively target mitochondria with cationic nMOFs for enhanced cancer therapy via RT-RDT with low doses of deeply penetrating X-rays.

Photoinduced Oxygen Evolution Catalysis Promoted by Polyoxometalate Salts of Cationic Photosensitizers.

The insoluble salt Cs15K[Co9(H2O)6(OH)3(HPO4)2(PW9O34)3] (CsCo9) is tested as heterogeneous oxygen evolution catalyst in light-induced experiments, when combined with the homogeneous photosensitizer [Ru(bpy)3]2+ and the oxidant Na2S2O8 in neutral pH. Oxygen evolution occurs in parallel to a solid transformation. Post-catalytic essays indicate that the CsCo9 salt is transformed into the corresponding [Ru(bpy)3]2+ salt, upon cesium loss. Remarkably, analogous photoactivated oxygen evolution experiments starting with the [Ru(bpy)3](5+x)K(6−2x)[Co9(H2O)6(OH)3(HPO4)2(PW9O34)3]·(39+x)H2O (RuCo9) salt demonstrate much higher efficiency and kinetics. The origin of this improved performance is at the cation-anion, photosensitizer-catalyst pairing in the solid state. This is beneficial for the electron transfer event, and for the long-term stability of the photosensitizer. The latter was confirmed as the limiting process during these oxygen evolution reactions, with the polyoxometalate catalyst exhibiting robust performance in multiple cycles, upon addition of photosensitizer, and/or oxidant to the reaction mixture.